Neurological complications associated with retrovirus-induced malignant disease, such as AIDS-associated encephalopathy caused by human immunodeficiency virus type I (HIV-I) infection and myelopathy associated with human T-cell leukemia virus type I (HTLV-I) infection, are becoming major concerns for human health. In order to elucidate the molecular mechanism for retroviral neuro-pathogenesis, we have been carrying out studies using rodent model systems. PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV that causes neurodegenerative disease in rats and mice. We have previously shown that there is a correlation between capillary endothelial cell (CEC) tropism of the virus and its neuropathogenicity, suggesting that virus-infection of brain CEC is necessary for induction of neuropathological changes. In this work, we have shown that Gly-116 and Lys-129 of the envelope SU protein of PVC-211 MuLV are major determinants for CEC tropism of the virus. We have also shown that PVC-211 MuLV can infect Chinese hamster ovary(CHO)-derived cells, which are normally resistant to ecotropic MuLV infection, and that the two amino acids important for viral CEC tropism confer a significant level of CHO cell tropism on the virus. These results suggest that the amino acids at positions 116 and 129 of the viral SU protein may play a significant role in virus-receptor interaction. In the course of these studies, we established a cell line, RTEC-6, from a primary culture of rat brain CEC. In this work, we showed that interleukin 6 (IL-6) gene expression in RTEC-6 cells is induced by lipopolysaccharide (LPS). The result enables us to use RTEC-6 cells for testing the effects of PVC-211 MuLV infection and human retroviral proteins on IL-6 expression by CEC. As one approach, we have constructed retroviral vectors for expressing the HIV-I tat gene, the HTLV-I tax gene, and transduced RTEC-6 cells with these vectors. Since it is possible that abnormal production of inflamma- tory cytokines, such as IL-6, by CEC is involved in the neuropathogenic mechanism, the result of this study may give useful insights into the molecular mechanism for retroviral neuropathogenesis. The intriguing CEC tropism of PVC-211 MuLV led us to initiate an attempt to establish a system for CEC-targeted gene therapy. For this purpose, we first analyzed the factors that affect the efficiency of retrovirus-mediated gene transduction into cultured CEC. Although CEC are rather refractory to MuLV-mediated gene transduction, treatment of cultured CEC with 2-deoxyglucose and vector inoculation in the absence of heparin significantly increased the transduction efficiency. This protocol may be useful for ex vivo gene transfer into CEC to generate animal models for CEC- targeted gene therapy.